The effect of high-pressure processing (HPP), microwaves (MWs), and their combination on the quality attributes and glucoraphanin−sulforaphane system of broccoli florets was investigated. The optimum HPP condition was a 3 min treatment at 400 MPa, which effectively reduced the growth of total aerobic bacteria, coliform, mold, and yeast, destroyed the surface structure, and enhanced the antioxidant capacity and sulforaphane production of florets. MW treatment increased the greenness (−a*) and antioxidant capacity, while heating at 462 W for 20 s resulted in the highest sulforaphane content in control florets. A loss of antioxidant capacity and an increase in yellowness (b*) were observed in 400 MPa treated florets after several MW treatments. Both 400 MPa and MW treatment promoted the exudation of glucoraphanin and synergistically activated myrosinase; thus, their combination led to a higher yield of sulforaphane after hydrolysis for 10 min or chewing for 30 s. The results indicated the combination of HPP and MW significantly improved the enrichment of sulforaphane in florets and the effective consumption of broccoli as a functional food.