SR 111's northern terminus is at Interstate 10 at the northwestern corner of the Palm Springs city limits, near the unincorporated community of Whitewater.

Since then, traffic heading to the border diverts from SR 111 onto westbound East Second Street to the port of entry's new facilities at Cesar Chavez Boulevard.

There, it intersects with Interstate 8 (I-8), which runs east to Yuma and west to San Diego, before passing through the agricultural communities of Holtville, Brawley, Calipatria and Niland.

Though some small settlements and a California state park line the shore, the area is eerily empty due to the sea's rapidly declining water quality.

SR 111 continues northwest as a major arterial road, four lanes or wider, through Indio, La Quinta, Indian Wells, Palm Desert, Rancho Mirage, and Cathedral City.

The highway transitions from an arterial road to a divided expressway as it exits Palm Springs just northwest of San Rafael Drive.

[citation needed] A 1993 rerouting of the highway takes drivers away from the historic center of Palm Springs, but meets with its original alignment as Business Route 111 a few miles further south.

The northern terminus was so busy in the 1950s before the construction of the freeway that visitors returning home to Los Angeles might have waited as long as two hours to make the left turn on the two-lane road that was once multiplexed as US Highways 60, 70 and 99.

The legislature opted to make the act an "urgency statute", effective immediately, so that the local governments could improve traffic bottlenecks along the route as soon as possible.

[10] The stretch through Rancho Mirage, which the city still calls "Highway 111" regardless of the relinquishment, has the Coachella Valley's only synchronized traffic lights; they are set to 45 mph (70 km/h).

[14][15][16] In a similar move in December 2005, the stretch of SR 111 through La Quinta was named the "Deputy Bruce Lee Memorial Highway".

[17] In September 2019 Caltrans began a three-phase $19[18]-21.5[19] million mitigation project to protect SR-111 from a moving mud pot called the Niland Geyser, southeast of the Salton Sea near the junction with Davis and Gillespie Roads.