Its southern terminus is at I-75 near Palmetto, where I-275 heads west towards the Sunshine Skyway Bridge crossing over Tampa Bay.

I-275 immediately heads west of its parent Interstate and has an interchange with US Highway 41 (US 41) two miles (3.2 km) up the road.

I-275 then has a major interchange with I-175, which provides access to Albert Whitted Airport and Tropicana Field, home of the Tampa Bay Rays.

[4] The next major interchange occurs less than a mile (1.6 km) down the road with I-375, providing access to the waterfront along Tampa Bay.

The freeway widens to four lanes in either direction at exit 30 before reaching its last interchange in St. Petersburg with SR 687 (4th Street).

After this major exit, I-275 reaches an interchange with US 92 (Hillsborough Avenue) again, allowing access to US 41, the historic Seminole Heights neighborhood, and East Tampa.

After this interchange, US 41 (Nebraska Avenue) acts as a parallel local arterial for the freeway throughout the rest of its route through Tampa.

[2] I-275 originally opened in 1962 as a segment of I-75, from the present northern terminus to a diamond interchange at SR 678 (Bearss Avenue).

In 1965, the segment of I-75 from "Malfunction Junction" to about Sligh Avenue was completed, and, by 1967, the remaining gaps in I-4 and I-75 were filled and opened to traffic.

The first setback was led by 4th Street business owners and residents who demanded that construction on I-75 be stopped, since the bridge was already funneling unwanted traffic into the corridor.

Around this time, I-75 was redesignated as I-275, and, after some more local opposition, I-275 was constructed to meander down to SR 595 (5th Avenue North), near downtown St. Petersburg, in 1975.

The construction of I-275 over nearly a 50-year period between 1970 and 2016 uprooted many Black families in the Methodist Town, Gas Plant, and 22nd Street neighborhoods.

These practices of eminent domain by the St. Petersburg government helped to shut down small companies in these neighborhoods and sustained white businesses that were located more centrally.

[9] Families in the Gas Plant neighborhood were assured good jobs at Tropicana Field to help ease the burden of moving.

[12] The families in the bulldozed Gas Plant neighborhood were guaranteed cheaper homes and 600 new jobs by the city, but these offers were never delivered.

In 1977, Chester James was appointed by the city government as the representative from Methodist Town to vote on the future development plans of his neighborhood.

At about the same time this interchange opened, I-275 was completed from the Sunshine Skyway Bridge to the southern terminus with I-75 in Manatee County.

Both interchanges underwent drastic changes to allow safe, free-flowing movement to and from Tampa International Airport, the Courtney Campbell Causeway, and the future Veterans Expressway.

The hiatus ended in 1999, when a much needed, dual-stage, widening project took place between SR 580 (Busch Boulevard) and Bearss Avenue.

The project widened I-275 mainline from four to six lanes, rehabilitated the existing concrete surfaces, and improved interchange flow, lighting, signage, and drainage.

The Ulmerton Road and 9th Street North interchanges were originally narrow 1959 configurations that caused much congestion in the area.

These interchanges were reconstructed into right-lane configurations, and two new ramps were added from Ulmerton Road (one leading to 9th Street North and one exiting onto southbound I-275).

The project consisted of widening mainline I-275 and I-4, along with an array of ramp and bridge improvements, lighting and drainage work, and new signs.

Construction began on phase one, the northbound lanes (south of the existing interstate) between Himes Avenue and Downtown Tampa, on August 13, 2007, and was completed in April 2010.

[15] Phase two, which includes construction of the northbound lanes from the Westshore area to Himes, was originally scheduled to begin in 2008 but was delayed further.

[21] Other sections not requiring a full-scale reconstruction have undergone improvements: The segment of I-275 in Manatee County has not changed dramatically since its construction in 1983, other than a toll plaza upgrade in the late 1990s and resurfacing of the mainline lanes between the I-75 apex and the US 19 exit.

In November 2005, The Florida Legislature dedicated the section of I-275 in Pinellas County as the "St. Petersburg Parkway/William C. Cramer Memorial Highway".