The highway runs for 369 miles (594 km) from a junction with Interstate 10 near Quartzsite to the New Mexico state line near Springerville.

As US 60 enters the Phoenix metropolitan area, It intersects Loop 303 in Surprise where it becomes Grand Avenue as it continues southeast.

The highway enters the Phoenix city limits and continues towards the southeast until it reaches an interchange with 27th Avenue near Thomas Road.

Improvements to the Grand Avenue portion of US 60, which were included in the Maricopa Association of Governments' 20-year Regional Transportation Plan, have been made.

After briefly heading south along 27th Avenue, US 60 turns left onto Thomas Road for 1⁄4 mile (0.40 km) until it reaches I-17.

After the curve, I-10 and US 60 part ways in Tempe, with I-10 continuing towards the south and US 60 now heading east along the Superstition Freeway.

The freeway enters the city limits of Apache Junction in Pinal County as it continues eastbound.

The highway continues towards the southeast passing through Gold Canyon to an interchange with SR 79 at Florence Junction.

Within the reservation, the highway goes through a series of hairpin turns as it enters the Salt River Canyon.

After descending into the canyon, the highway passes over the Salt River and enters the Fort Apache Indian Reservation.

US 60 continues towards the east leaving the Springerville city limits and crossing over the state line into New Mexico.

[12] US 60 through Arizona has had far fewer major changes than some other U.S. routes, but one notable example is being replaced by Interstate 10 between Los Angeles, California, and the highway's current terminus near Quartzsite.

Due to rapid growth in the far eastern Phoenix suburbs within Pinal County and increasing road congestion in the Gold Canyon area, ADOT has begun to study potential freeway-grade realignments of US 60 past the current eastern terminus of the Superstition Freeway in Apache Junction.

The new freeway alignment would bypass the existing at-grade section of US 60 through Gold Canyon, and would either rejoin the existing alignment southeast of town (in the vicinity of the Arizona Renaissance Festival grounds) or at the newly constructed freeway-grade junction with SR 79 at Florence Junction.

[18] Notes An unsigned U.S. Route 60X is also listed by ADOT and is divided into two discontinuous segments, both of which are located within Maricopa County in the Phoenix area.