Players can progress through the story by completing quest scenarios with set goals. In addition to doing missions, players are free to wander the open world - from the open countryside of Blaine to the fictional city of Los Santos. Grand Theft Auto V's maps are larger than any of the earlier entries in the series. Maps are unrestricted to explore from the start, but more gameplay is unlocked as the storyline progresses. Players use fist and foot melee attacks, guns, weapons, and bombs to fight enemies, and are able to navigate the map by running, jumping, swimming, and driving various vehicles. To accommodate the size of the map, the game introduces fixed-wing aircraft that were absent in Grand Theft Auto IV. The game offers an auto-targeting and dodging system to help players fight enemies. If the main character is injured, his health will be restored to the midpoint. The player advances the game's story by completing a series of missions, and as with most open-world games, the player is free to perform these missions at any time they choose. If the player commits any in-game violations, the game's police agency may take action and the player's "wanted" status will be displayed in the upper right corner of the game. As the player continues to break the law, the asterisk representing the wanted level will increase and the police pursuit of the player will become more intense.

With one star, the police will attempt to arrest the player, and if the player is arrested, he or she will be required to pay bail and have all weapons, ammunition, and armor confiscated at the time of arrest. If the player resists arrest or makes the police feel aggressive (such as shooting in front of the police) then it becomes two stars and the police will start shooting to try and kill the player instead of arresting. If the player kills the police, the player will become three stars, then there will be a police helicopter with two shooters and a wider search area to support, and there will be police vans on the road to place chicken claw spikes to block the player, making it more difficult for the player to escape from the wanted. If the player destroys the police helicopter (usually 2) or continues to commit crimes, attacks the police, and at any point enters the Sankudo Fortress, Bolingbrook Prison, with three stars, he will become a four-star, when the NSA officers equipped with carbine rifles will ride (not sit inside) the FIB official car or join the battle by dropping the helicopter. When the player continues to commit crimes for a period of time after the four stars then the game's highest stat level of five stars will be reached, at which point the proportion of NSA officers will be significantly higher (at four stars there are more general police officers), roads will be traffic controlled (there will only be police officers or vehicles on the road, hardly any civilians), the number of vehicles in pursuit will increase significantly, and helicopters will be changed from one to two (maximum three).

After the player escapes from the police line of sight, the wanted star in the upper right corner will start blinking and will be cancelled after blinking for a period of time and not detected by the police (the police line of sight is the blue area on the mini-map). In the past, if the player was wanted, he could avoid the police by modifying the car or hiding in a safe house, but in this game, the car modification store will be closed for a short time while the player is wanted by the police, and even if he hides in a safe house, he will continue to be pursued by the police. Unlike the previous game there is no place to get stars to reduce the degree of being wanted. So this game needs to completely escape from the police's sight range before the wanted will be canceled. However, as in the past, players can enter the safe house to rest (i.e. "store the game") after the wanted order will be canceled, but three stars or more can not be "store the game" action. At the same time, players can not use weapons indoors, but if the wanted star number is three stars or more will be able to use weapons indoors.

In the single-player mode, players take on the roles of the three main characters in Grand Theft Auto V, namely Michael De Santa, Franklin Clinton and Trevor Philips, whose stories will gradually intertwine and overlap as the missions progress. Some tasks can only be completed by one person, some can be freely switched between the three main characters. The switch is made using the on-screen character orientation compass, which has four fields: Franklin on the top, Mike on the left, Trevor on the right, and the player's own character in the online multiplayer mode (or the character in use if in director mode) on the bottom. During missions, the /game sometimes automatically switches between characters in order to achieve a specific purpose. When a character is in danger of needing help, the image on the compass representing that character will flash red, while if the character is in a strategically advantageous position, the image will flash white, a system that helps the player complete the mission successfully. As the game's missions are completed, more difficult heist missions will appear and may require additional computer-controlled characters to help complete them. These secondary characters have unique skills, such as hacking or driving, and they will also share a portion of the loot with the protagonist after the mission is completed. If the secondary characters survive the heist, their special skills will improve and they will be able to work together again on the next heist. The game also encourages the player to use different strategies to complete the heist, for example, the player can choose to use disguise to sneak into the target location of the heist, or force entry by force.

Each character has eight skills that cover their abilities in specific areas, such as shooting and driving, and each skill will be improved during play, while each protagonist also has their own skills that they are better at, for example, Trevor's background as a pilot makes his flying skills better than the other two characters. In addition, each character also has their own "special skills". The eighth "special" skill determines the effectiveness of each character's ability to perform the skill. Mike can enter bullet time in battle, Franklin can slow down time while driving, and Trevor can double the attack power and significantly reduce damage in battle. [27] The flat screen display has a special ability bar that will gradually decrease when used and will gradually return when not used. In the carrier, driving in the opposite direction, quickly cutting through the workshop and other actions can make the special ability bar increase quickly.

Players can take on specific activities such as scuba diving and skydiving as they wander the game world. Each character can contact friends, conduct activities, and browse the game's "website" via smartphone. Players can buy and sell stocks online. In online mode, players can also purchase home and business properties, upgrade weapons and vehicles in each character's arsenal, and purchase clothing, hairstyles, tattoos, and jewelry to customize their appearance.

Developed in conjunction with the single-player mode, the multiplayer online mode Grand Theft Auto Online is a solo experience alongside the ever-changing world. Up to 30 players are free to roam the recreated single-player world and enter lobbies to complete jobs (plot-driven competition and co-op modes). Content builder kits allow players to customize careers, such as weapon respawn points for racetracks and deathmatches. Players can organize gangs to collaborate on jobs, and the Rockstar Games Social Club expands to the online version with gangs formed by Max Payne 3. Players can create their own gangs or join up to five gangs. Gangs can earn experience and improve online rankings by completing multiplayer events