It begins at a partial interchange with US Highway 1 (US 1) just south of downtown Miami and heads north through Jacksonville, and to the Georgia state line at the St. Marys River near Becker.

[2] Additionally, I-95 north to West Palm Beach, as well as SR 9 southwest to 27th Avenue, runs parallel to the Seaboard–All Florida Railway, used by CSX Transportation for cargo and freight, Tri-Rail for commuter rail, and Amtrak's Silver Star (temporarily replaced by the Floridian) and Silver Meteor lines for intercity rail.

Both freeways eventually go separate ways north of Fort Pierce; I-95 continues directly along the coast; Florida's Turnpike turns west toward Orlando.

The road soon enters Indian River County and the next major exit is with SR 60 providing access to Vero Beach.

The highway soon enters Brevard County and the Space Coast of Florida, continuing past Melbourne, Viera, and Cocoa.

Continuing north past Titusville, I-95 enters Volusia County and the city of Daytona Beach shortly afterward, where it meets with the eastern terminus of I-4.

The Interstate passes through the heart of Jacksonville, crossing the Fuller Warren Bridge over the St. Johns River, which was rebuilt from its original drawbridge incarnation in 2002.

About a mile (1.6 km) north of the bridge, at exit 351B, it intersects with the national eastern terminus of I-10, with the interchange's redesign completed in September 2010.

By 1976, most of the highway was complete from the Georgia state line to Fort Pierce as well as Palm Beach Gardens to Miami.

[11][12] In the mid-1960s, the State Road Department authorized traffic counts be conducted to determine if the separation of I-95 from the turnpike was feasible, with arguments that using a concurrent alignment was costing Florida money for federal highway funding, but not without the concern of losing toll revenue.

[14] Over time, the Interstate adopted a separate route closer to US 1, running parallel with the turnpike between Stuart and Palm Beach Gardens, and was originally scheduled to be completed in 1972.

However, resistance by Martin County officials due to environmental and unwanted growth concerns delayed the highway's completion for 15 years, requiring those who wanted to travel through the Treasure Coast to take either the slower US 1 or the tolled turnpike.