Born in New York City, Pike first rose to prominence playing for the Philadelphia Athletics, who he joined in 1866. He brought an impressive blend of power and speed to the team, hitting many home runs as well as being one of the fastest players around. However, it was soon brought to light that he and two other Philadelphia players were being given $20 a week to play. Since all baseball players were ostensibly amateurs (though many were, like Pike, accepting money under the table), a hearing was set up by the sport's governing body, the National Association of Professional Baseball Players. In the end, no one showed up to the hearing, and the matter was dropped. By 1869, the Cincinnati Red Stockings would become the first openly professional team, and Pike's hearing, farcical as it seems to have been, paved the way for Harry Wright's professionalization of baseball.

The Athletics were very successful, but Pike was dropped from the team in 1867, because he was from New York, and thus a 'foreigner', calling his loyalty into question. He moved on to the New Jersey Irvingtons and later the New York Mutuals, having caught the eye of Boss Tweed, and enjoyed continued success closer to home. In 1869, he moved to the Brooklyn Atlantics, one of the top teams in baseball at the time. In 1870, the Atlantics, with Pike manning second base, finally ended Cincinnati's 93-game winning streak.

In 1871, the National Association was formed as the first professional baseball league, and Pike joined the Troy Haymakers for its inaugural season. He was their star and captain, and proved equal to the task, batting .371 and hitting a league-leading 4 home runs. He also led the league with 21 extra-base hits and his .654 slugging percentage was good for second. The Haymakers only finished sixth, though, and the team's captaincy switched to Bill Craver after a bad run.

The Haymakers completely revamped their roster for the 1872 season, and Pike headed for Baltimore, where he played for the Baltimore Canaries. The Canaries finished third in the league, and Pike had another excellent season, leading the league in home runs again, with six, and also in RBI, with 60. In 1873, the Canaries again finished third, helped by the addition of Cal McVey as captain and catcher from the dominant Boston Red Stockings, and Pike led the league in home runs for the third consecutive season, hitting 4. Baltimore went bankrupt after the season, so Pike headed off to captain the Hartford Dark Blues for the 1874 season. The Dark Blues were a poor team, and only finished seventh, but Pike had another fine season, slugging .574 to lead the league, and coming in second with an on base percentage of .368.

Pike abandoned the weak Hartford team after a single season, switching to the St. Louis Brown Stockings. St. Louis finished a respectable fourth, although Hartford, under the direction of former Atlantic teammate Bob Ferguson, finished third. For the first time in his professional career, Pike failed to hit a home run, although he stole 25 bases. He also hit 12 triples and 22 double in what was probably his finest offensive season. In 1876, when the National League replace the National Association, Pike stuck with St. Louis. The Brown Stockings turned in a very good season, finishing a solid second to the Chicago White Stockings, who had taken the best players from the powerhouse Boston teams of the previous years. Pike continued to produce offensively, notching totals of 133 total bases (5th in the league) and 34 extra-base hits (2nd).

Seemingly never content to stay with a team very long, Pike headed to the Cincinnati Reds for the 1877 season. The Reds were another bad team, and they finished last. Pike was still a top-quality player, leading the league in home runs for the fourth time in the 1870s. However, age was starting to catch up with the 32 year-old Pike. He began the season as the eighth-oldest player in the league, and was the fourth oldest player of the 1878 season. The Reds of 1878 played very well, though, having added Cal McVey, King Kelly, and Deacon White. They finished second, but Pike was replaced by Buttercup Dickerson halfway through the season and Pike was forced to look elsewhere for a team. He ended up playing a few games for the Providence Grays.

Pike spent the next two years playing for minor league teams. He got a brief call-up in 1881 to play for the Worcester Worcesters, but the 36 year-old Pike could no longer play effectively, hitting .111 and not managing a single extra-base hit in 18 at-bats over 5 games. His play was so poor as to arouse suspicions, and Pike found himself banned from the National League that September. He turned to haberdashery, the vocation of his father, and spent another six years playing only amateur baseball. In 1887, the New York Metropolitans of the American Association gave Pike another chance. The only game he played was more of a sending off than a new start, though, and Pike headed back to his haberdashery once more. On October 10, 1893, Lip Pike died of a heart disease at the age of forty-eight. He was interred in the Salem Fields Cemetery in Brooklyn, New York.

Lip Pike was one of the premier players of his day. He was a great slugger and one of the best home run hitters of his day, so much so that stories about balls he hit were told for quite some time after he stopped playing. He was also one of the fastest players in the league. He would occasionally race any challenger for a cash prize, rountinely coming out the winner. On August 16, 1873, he faced a trotting horse in a hundred-yard sprint, and won, earning $250. He was also the first famous Jewish baseball player, and has been inducted into the International Jewish Sports Hall of Fame. In 1936, long after the players he faced had retired, and 43 years after his death, Pike received a vote for the Baseball Hall of Fame in its first election. Although it was only a single vote, the memory of his deeds on the diamond was strong enough that he was remembered nearly 60 years after his last great season.