Fatigue cracking and transverse cracking are two of the most prevalent distresses in flexible pavements. In this study, probable causes of these distresses were evaluated using field and laboratory testing and simulations using AASHTOWare Pavement ME Design (PMED). For this purpose, three pavement test sections, located in US 270, US 287 and US 412 in Oklahoma, were selected. The test sections in US 270 and US 287 have experienced significant transverse cracking, while the test section in US 412 has seen major fatigue cracking. A series of non-destructive and destructive testing involving Ground Penetrating Radar (GPR), Falling Weight Deflectometer (FWD) and Dynamic Cone Penetration (DCP) was performed at each test section. Also, soil samples and asphalt cores were collected for laboratory testing. In US 270 and US 287, numerous transverse cracks were found to extend full width of the pavement, including shoulder indicating that these transverse cracks resulted from thermal cracking. Analysis of weather data from nearby climate stations indicated a large number of low-temperature events, high temperature differential cycles and hourly temperature fluctuations. These factors were a likely contributor to thermal cracking at both sites. The PMED simulations supported these findings. Field and laboratory testing indicated that severities of transverse cracking were influenced by high variations in asphalt layer moduli, pavement thicknesses and low cracking resistance of both pavements, in addition to extreme low temperature events and temperature differentials. The GPR tests indicated that pavement thickness varied along longitudinal and transverse directions and cracks initiated from the surface and propagated downward through the entire asphalt layer(s) at both sites. The FWD and DCP tests revealed that both pavement sections were structurally adequate to support the existing traffic for ten plus years, with appropriate maintenance. However, FWD results indicated high variations in asphalt layer moduli throughout the pavement section, at both sites. The Illinois Flexibility Index Test (IFIT) on the extracted cores from both sites indicated that stiffer and brittle asphalt mixes resulting from aging during the long service life were a major contributor to transverse cracking at both sites. A parametric study and sensitivity analysis using PMED simulations indicated that binder grade and pavement thickness were the most influential factors for transverse cracking at both sites. In US 412, GPR tests revealed significant delamination, top-down fatigue cracking, bottom-up fatigue cracking and variations in pavement thickness in both longitudinal and transverse direction. Also, GPR images indicated that the disturbance zone was confined within the asphalt layer. Physical inspection of asphalt cores and core-holes validated these findings. Stripping was found to worsen the delamination at several locations. Analysis of FWD data indicated that the pavement section in US 412 was structurally inadequate to support traffic and is in need of rehabilitation in the near future. Also, variations in moduli of the asphalt layers and high deflections of geophone sensors were observed from the field FWD tests at this site. Roadway density tests indicated very low densities of asphalt cores of the pavement than expected. In addition, true PG of the extracted binder indicated excessive aging of the binder at this site. Furthermore, IFIT tests revealed very poor cracking resistance of the field cores. Therefore, delamination, variations in layer moduli, variations in pavement thickness, low roadway densities, excessive aging of binder and poor cracking resistance were found to be potential contributors to fatigue cracking at this test section. In addition, PMED simulations indicated pavement thickness, high-temperature performance grade of binder, roadway densities and layer moduli of the existing pavement were influential factors for fatigue cracking at this site. The hybrid approach involving laboratory and field testing and PMED simulations is found to be an effective tool for identifying probable causes of transverse and fatigue cracking in asphalt pavements. Assessment of these distresses using this hybrid approach would be helpful in designing new pavements as well as in selecting remedial measures of existing pavements.