Heavy-duty diesel trucks (HDDTs) comprise a key source of road transport emissions and energy consumption worldwide mainly due to the growth of road freight traffic during the last two decades. Addressing their air pollutant and greenhouse gas emissions is therefore required, while accurate emission factors are needed to logistically optimize their operation. This study characterizes real-world emissions and fuel consumption (FC) of HDDTs and investigates the factors that affect their performance. Twenty-two diesel-fueled, Euro IV to Euro VI, HDDTs of six different manufacturers were measured in the road network of the Hong Kong metropolitan area, using portable emission measurement systems (PEMS). The testing routes included urban, highway and mixed urban/highway driving. The data collected corresponds to a wide range of driving, operating, and ambient conditions. Real-world distance- and energy-based emission levels are presented in a comparative manner to capture the effect of after-treatment technologies and the role of the evolution of Euro standards on emissions performance. The emission factors’ uncertainty is analyzed. The impact of speed, road grade and vehicle weight loading on FC and emissions is investigated. An analysis of diesel particulate filter (DPF) regenerations and ammonia (NH3) slip events are presented along with the study of Nitrous oxide (N2O) formation. The results reveal deviations of real-world HDDTs emissions from emission limits, as well as the significant impact of different operating and driving factors on their performance. The occasional high levels of N2O emissions from selective catalytic reduction equipped HDDTs is also revealed, an issue that has not been thoroughly considered so far.