Reuters/Jonathan Alcorn
Officers in riot gear ordered the crowd of about 1,000 protesters to disperse, shortly after the rally ended.
They declared the gathering an unlawful assembly soon after.
At least 18 people received medical attention, according to The San Diego Union-Tribune.
One protester was arrested after trying to climb a barrier separating protesters from police, several news outlets reported. His arrest led protesters to throw empty water bottles and spray water at police. At least three people were arrested, according to the San Diego Police Department.
Many of the protesters waved US and Mexican flags and chanted in Spanish, prompting Trump supporters to yell "Speak English" and "Go back to Mexico."
CNN captured some of the action:
Pro-Trump and anti-Trump groups clash in San Diego. @pvercammencnn is on the ground with the latest. https://t.co/1EDxruPvDD
- Anderson Cooper 360° (@AC360) May 28, 2016
The incident comes just two days after 14 protesters were arrested at a Trump rally in Anaheim.
The presumptive Republican nominee has come under fire for his immigration policies, which include building a wall along the southern US border with Mexico and deporting the nearly 11 immigrants who are in the US illegally.
California is home to the largest Latino population in the US, and one of the crossings along the San Diego-Tijuana border is considered the busiest in the world.