Fresh market spinach has one primary herbicide, cycloate, which does not control all weeds. Previous studies demonstrated that cycloate PRE followed by (fb) phenmedipham at the four-leaf spinach stage is a safe and effective treatment. However, this treatment is not useful for the main growing season of fresh spinach due to its short crop cycle and the 21-d preharvest interval requirement of phenmedipham. This study evaluates the potential to use the combination of cycloate PRE fb phenmedipham on two-leaf spinach. Greenhouse and field studies were conducted in 2014 using three spinach varieties with low (‘Nordic' and ‘Sardinia') and high (‘Regal') tolerance to phenmedipham. Greenhouse studies revealed that phenmedipham at 90 g ai ha−1 was safe to Regal when applied at the two-leaf stage. Sardinia was more susceptible to phenmedipham injury under high (310 W m−2) light conditions than low (258 W m−2) light conditions. Impact of time of day on phenmedipham safety was evaluated in the field: day-long exposure to high light intensity following morning applications vs. evening applications fb exposure to low light intensity. Injury estimations taken 3 d after treatment (DAT) were lower for evening than for morning applications. Nonetheless, injury 11 DAT and spinach yield evaluations found no differences between morning and evening applications. Subsequently, cycloate (1,700 g ha−1) PRE fb phenmedipham (90 and 180 g ha−1) applied in the evening at the two-leaf stage was evaluated. A reference treatment was cycloate PRE fb phenmedipham (270 g ha−1) at the four-leaf stage. Treatments with cycloate fb two-leaf phenmedipham at 90 and 180 g ha−1 were safe to spinach and improved weed control compared to cycloate alone. Cycloate fb 180 g ha−1 phenmedipham at the two-leaf stage reduced weed biomass by 88% compared to cycloate alone. This level of weed control was similar to the reference treatment. Results here show that phenmedipham applied at the two-leaf stage is safe to fresh market spinach and it has the potential to be used during most of the fresh spinach growing season.