In addition to Arecibo, Aguadilla, and Mayagüez, the road runs through various other cities including Guaynabo, Bayamón, San Germán and Yauco.

Puerto Rico Highway 2 starts off in San Juan as an 8-lane road and heads west roughly parallel to the northern shore of the island.

In addition to numerous residential communities, PR-2 also provides access to malls, movie theaters, restaurants, hospitals, and various colleges and universities, among other facilities in this area.

Continuing west, Puerto Rico Highway 2 next serves the industrial towns of Manatí and Barceloneta providing access to several pharmaceutical companies, among other sources of employment outside the agricultural sector.

The trip from Aguadilla to Mayagüez takes about 30 minutes, and PR-2 has fewer traffic lights in this stretch of the road than those experienced so far anywhere from its San Juan terminus starting point.

Also, further south, PR-2 provides access to the Mayagüez Mall, which is Puerto Rico's third largest shopping center[citation needed] and several medical facilities.

As the road makes its way through the hills of Peñuelas' barrio Tallaboa, the ruins of the abandoned 1970s CORCO oil refinery as well as its PPG supplier are visible to the right.

It provides access to four of Ponce's beaches, to the Damas and Dr. Pila hospitals, to various shopping plazas including the Plaza del Caribe Mall and Centro del Sur Mall, the Puerto Rico Judicial Center, the University of Puerto Rico at Ponce, the Mercedita Airport, and numerous restaurants and other facilities.

The PR-2 segment corresponding to the city of Ponce was built in the late 1940s and is known as the "Ponce By-Pass",[2] since it was used to "bypass" the urban and commercial city center when traveling due east from western towns such as Guayanilla, Yauco, San Germán, and Mayagüez, to towns in eastern Puerto Rico such as Salinas, Guayama, Cayey, Caguas, and San Juan.

After this dual intersection at PR-133/PR-1 the road seamlessly becomes a 4-lane thoroughfare called Miguel A. Pou Boulevard, the city's main artery into the Ponce Historic Zone.

In this stretch, during the mid 2000s to early 2010s, the Puerto Rico Department of Transportation and Public Works (DTOP) converted most segments of PR-2 between Mayagüez and Ponce into a limited access expressway.

The segment between Hormigueros and San German, in particular, suffered from several at-grade intersections that slowed down travel time considerably.

In an effort to increase the controlled access, freeway-style character of the highway, all at-grade intersections were either replaced by overpasses or eliminated altogether.

This would occur between the future western terminus of Puerto Rico Highway 22 in Aguadilla to the Mayaguez city limits.

[9] The PR-22 extension to Aguadilla was planned for completion in 2016,[9] and freeway conversion of the Aguadilla-to-Mayaguez segment of PR-2 was slanted to begin shortly afterward.

Due to the high population density on the northern coast of Puerto Rico, a new, limited access expressway, PR-22 (also known as Autopista José de Diego), was built parallel to highway PR-2.

The entirety of its segment in Mayagüez was formerly known as Calle Post, until recently when it was renamed into two names, under the José Guillermo Rodríguez administration.

As the longest street in Mayagüez, served as main entrance to the center of the city and gave access to some communities as Colombia, Santurce, Belmonte, Cuesta de las Piedras, Río Cristal and Barriada Nadal (Poblado Sábalos).

Originally named by governor Regis Henri Post in 1909, it was recently renamed both honoring Alfonso Valdés Cobián and Ramón Emeterio Betances by disposition of the Municipal Legislative.

Going south the Yagüez River comes inside the downtown of Mayagüez city, crossing the Méndez Vigo (PR-106), Candelaria (PR-105), Nenadich, Hiram David Cabassa, PR-348, PR-380, and Carolina roads to finally ending at the PR-2 aside with Avenida Corazones in Sábalos ward.

Also known as Carretera a Pámpanos, the north–south road runs for 1.9 km (1.2 mi)[18] and was the original PR-2 before the construction of the current alignment known as the Ponce By Pass.

[20] Located entirely within Barrio Canas, PR-2R begins at PR-2 in the south, in the Pámpanos neighborhood and, as you head north, it passes the Paquito Montaner Stadium and the Juan Pachín Vicéns Auditorium, both to the left.

PR-2R then passes Escuela Superior Vocacional (Vocational High School) to the right and Secretaría de Recreación y Deportes Francisco "Pancho" Coimbre to the left, where it intersects with PR-163 (Avenida Las Américas).