Only when the road enters Middleburg does SR 21 become a four-lane divided highway just south of the intersection of CR 215 (Kingsley Lake Road), and curves to the northeast again. From here it gains the name Blanding Boulevard from here to its northern terminus. It then crosses CR 218. Shortly after then it serves as the terminus of CR 220 (Everett Avenue), and begins a hidden concurrency with SR 21, and serves as the southern terminus of CR 220A (Long Bay Road) before CR 220 ends the concurrency at Doctors Inlet Road. SR 21 then encounters Branan Field Road, which becomes SR 23 to the north. An interchange between SR 21 and SR 23 is planned to be built slightly to the west of the current intersection as part of the First Coast Expressway. The road crosses CR 220A again at Old Jennings Road. Beyond that, it has two western termini with another suffixed route, known as CR 21B (Jefferson Avenue) in Ridgewood. In Lakeside, SR 21 serves as the northern terminus of CR 224 (College Drive), providing access to Saint Johns River Community College. CR 21B ends at SR 21 again along Cleveland Avenue. Near Orange Park, the road curves straight north again where SR 224 serves as the last major intersection before entering Jacksonville, although SR 21 passes through one more community known as Meadowbrook Terrace, the home of the Orange Park Mall. North of the Clay–Duval county line, SR 21 enters Jacksonville, and then approaches the interchange with I-295, which was recently redesigned to accommodate ramps to Collins Road, a street that intersects with SR 21 north of the interchange.