The Orange Line is San Diego’s second trolley line, with the first phase opening as the East Line between downtown San Diego and Euclid Avenue in 1986. The line was extended in a couple of phases to the El Cajon Transit Center in 1989, and around Downtown San Diego via the Bayside Line in Downtown San Diego on June 30, 1990.

Starting in 1990, and for the next 22 years trolleys made a bi-directional loop around downtown, with trains both stopping at and terminating at 12th & Imperial. El Cajon-bound Orange Line trains entered service on the Bayside terminus platforms at 12th & Imperial Transit Center, making 8 station stops while looping along the Bayside Line and via the regular Downtown line, stopping at 12 & Imperial Transit again before continuing east to El Cajon.

Orange Line service reached its maximum route length with an extension on the opposite end of the line with an extension to Santee Town Center on August 26, 1995.

The Orange Line is a rare fixed-guideway transit line to get shorter in the 21st century, primarily caused by the introduction of the Green Line. When this route was introduced in 2005, at first it took over service only to the former last stop on the Orange Line, Santee Town Center, with trains pushed back to Gillespie Field.

On September 2, 2012 were the most significant shortenings to the Orange Line, Green Line trains were extended downtown taking over Orange Line service at the 4 stops on the Bayside Connector, and pushing Orange Line trains back to terminating in Downtown to now terminating at Santa Fe Depot. This service change also removed the unique loop feature of the Orange Line stopping at 12th & Imperial before looping around to terminate it. On the opposite, eastern end of the line, low-ridership (and the Green Line now also providing service to Downtown) pushed Orange Line service back 2 stops on the shared section of track to El Cajon Transit Center.

Orange Line service through downtown kept getting shorter, on June 11, 2017 Orange Line trains were pushed across the street from Santa Fe Depot to terminate with the Blue LIne at America Plaza, and then a couple of blocks further back on April 11, 2018 to the new Courthouse terminus, which is a newly built third siding track with a side platform for terminating Orange Line trains, alongside two through trolley tracks used by Blue Line trains that skip the station. The line did get re-extended at its western end one stop to Arlene Avenue on this same day, resulting in its current routing from Courthouse to Arlene Avenue.

For Rolling stock, the Orange Line originally used U2 trolleys, shared with the Blue Line, but the SD-100s started to be introduced for service expansions from 1992 to 1995, and these began to be the main trolleys used on the Orange Line. For ADA accessibility, both of these trolleys had on-board wheelchair lifts (like on a high-floor bus), that could only be deployed to the right of the trolley.

All Orange Line stations were rebuilt between 2011 and 2012 to have six inch tall platforms (Orange Line stations originally had primarily only 4 inch tall platforms, or passengers boarded trolleys at street level) to allow modern Low-Floor S70 Ultra Short trolleys to operate on the Orange Line. Starting in January 2013 Orange Line trains began running S70s, allowing a vastly more accessible riding experience with ADA riders able to board at most doors (using an automatically deployed ramp) instead of only at the front door and slowing down trolley service with the delays needing to use the wheelchair lift. At first trolleys operated as mixed-fleet trains with at least one S70 and an older (and no longer accessible) SD-100 as the the middle car on three car trains, or other car on two car trains. Throughout the next ten years, as addition S70 US (Ultra Short) and S700 US models (their slightly updated newer versions) have been delivered more and more fully low-floor trolleys have entered service, with the SD-100s slowly being retired, with the goal of an eventual full low-floor trolley fleet.