The objective of this research was to optimise the fresh mix properties, rheological parameters, heat of hydration and development of the compressive strength of cement mortars containing nano-clay (nCL) and fly ash (FA). All mixtures were made with water-to-binder ratio (W/B) of 0.40. The replacement of cement by FA was varied from 5% to 20% (by mass of cement), and dosages of superplasticiser (SP) and nCL were varied from 0.6% to 3% (by mass of binder), and 0.5% and 2.5% (by mass of cement), respectively. The fresh mix properties were evaluated by using mini-slump flow, Marsh cone flow time and Lombardi plate cohesion meter, and induced bleeding. Yield stress and viscosity were determined to analyse the effects on rheology. Variations in hydration kinetics were examined through calorimetry tests. Compressive strength was measured and evaluated at different ages up to 28 days. Dosages of nano-clay, fly ash and superplasticiser were the investigated key parameters. Statistical models and isoresponse curves were used to identify significant trends. Prediction models were developed for mini-slump, Marsh cone, Lombardi plate cohesion meter, heat of hydration, induced bleeding, static and dynamic yield stress, plastic viscosity, and compressive strengths at 1 d, 3 d, 7 d, and 28 d as function of nCL, FA, and SP. Optimization of mortar proportioning to fulfil required performance levels in fresh and hardened states was possible by using the predicted models presented in this paper.