In baseball, interference occurs in situations in which a person illegally changes the course of play from what is expected. Interference might be committed by players on the offense, players not currently in the game, catchers, umpires, or spectators. Each type of interference is covered differently by the rules.

The most common incidence of interference occurs when a member of the offensive team physically hinders the defensive team, decreasing its chances to make an out or increasing the chance that a baserunner will advance. Whenever this offensive interference occurs, the ball becomes dead. If the interference was committed by a batter or a baserunner, that player is called out and all other runners must return to the bases they occupied at the time of the interference. If interference is committed by a runner with the obvious intent of preventing a double play, the batter-runner will be called out in addition to the runner who committed the interference. If interference is committed by the batter-runner before they reach first base with the possible intent of preventing a double play, the runner closest to scoring is called out in addition to the batter-runner. If interference is committed by a retired runner or by some other member of the offensive team, the runner who is most likely to have been put out will be called out.

Under Little League (LL), high school (NFHS) and college (NCAA) rules, if interference is committed by a runner with the effect of preventing a likely double play, regardless of their intent, the batter-runner will be called out in addition to the runner who committed the interference.

Also under NFHS rules only, all runners are required to attempt to avoid collisions. If a runner fails to do so, they are guilty of malicious contact, which is one kind of offensive interference. Malicious contact carries the additional penalty of ejection from the game. In contrast, in professional and higher amateur baseball, violent collisions can occur without any interference (or obstruction), especially when a fielder is receiving a thrown ball near a base where a runner is trying to reach. Any collision that occurs in this situation is not interference, because the fielder's action is in regard to a thrown ball. As long as such a runner's actions are related to their attempt to reach the base, they cannot be called for interference. The most common case of this is when a runner is attempting to score and the catcher has control of the ball. If the catcher is in the path between third base and home plate, the baserunner may strike the catcher with their body in an attempt to dislodge the ball from the catcher's hand and then reach home plate. This is usually attempted only when the play is close. When the catcher is set up and ready, the runner has little chance of knocking the ball away. Any such attempt presents a significant chance of injury to the baserunner, which has prompted the malicious contact rule to be used more often. In addition to the general subjective definition of offensive interference, it is also interference by specific rule when:

There are some exceptions to the penalty for offensive interference.

At some levels of play, verbal as well as physical hindrance can be called for interference. For example, if a runner or other member of the offense calls out "foul" on a fair ball or "mine" on a fly ball, they may cause the defense to react differently from how they otherwise would have, resulting in an interference call. Some professional leagues do not have a distinction for verbal interference or obstruction and leave it as umpire judgement. The NPB in Japan, for example, verbal interference is illegal and runners will be called out on any spoken word meant to confuse a fielder or fielders during a play. In Major League Baseball, it is left as umpire judgement.

On October 15, 1969, in Game 4 of the 1969 World Series between the New York Mets and Baltimore Orioles, Mets pinch hitter J.C. Martin attempted a tenth-inning sacrifice bunt which Orioles pitcher Pete Richert fielded; however, Richert's throw to first base hit Martin on the wrist and the ball ricocheted into right field, allowing Mets baserunner Rod Gaspar to score the winning run from second base. The Orioles protested vehemently, but although replays showed Martin ran inside the first base line, umpires ruled the play valid and no interference was called. The win gave the "Miracle Mets" a 3–1 lead in the series, and they closed out their championship season with a win the next day.

An alleged offensive interference occurred in the third game of the 1975 World Series. With a runner on first, Cincinnati Reds player Ed Armbrister laid down a sacrifice bunt. Red Sox catcher Carlton Fisk attempted to field the ball and throw to second base and get the lead runner out. However, Armbrister did not immediately run to first base but instead stood essentially still in the vicinity of home plate, forcing Fisk to jump into him in order to make the throw. As a result, Fisk's throw went into center field, and the Reds ended up with runners on first and third with no outs. The Red Sox protested, saying that Armbrister interfered, but home plate umpire Larry Barnett refused to change the call. The rules at the time did not mention a batter-runner/catcher collision, but the official interpretation issued to the umpires did; there is no violation on such unintentional contact. The Red Sox lost the game, and the series.