Efficiently organizing molecular nonlinear optical (NLO) chromophores having large first-order hyperpolarizabilities (beta) into acentric microstructures for electro-optic (EO) applications represents a significant materials synthesis and processing challenge, in part due to interchromophore dipolar interactions that promote centrosymmetric organization. Here we report the computational modeling, synthesis, and characterization of a series of eight heteroaromatic organic chromophores, designed to self-organize from the vapor phase via directed hydrogen-bond networks, into acentric thin films. Introduction of alpha,omega-donor-acceptor hydrogen-bonding substituents along the molecular long axes tunes properties such as hyperpolarizability, volatility, thermal stability, film-forming properties, and macroscopic NLO response (chi((2))). DFT-level molecular modeling, INDO/S optical property analysis, and sum-overstates computation indicate that molecular-core fluorination and hydrogen-bond donor incorporation can increase beta(vec) up to 40x versus that of typical fluorine-free chromophores. Furthermore, inclusion of sterically induced biphenyl conjugative decoupling between chromophore pi-donor substituents and the hydrogen-bonding donor sites increases beta by similar to 50%. Experimental thin-film second harmonic generation (SHG) spectroscopy confirms these trends in calculated responses, with chi((2)) increasing 7.5x upon chromophore core fluorination and 15x with hydrogen-bonding donor substitution, thereby achieving macroscopic responses as high as 302 pm/V at omega(o) = 1064 nm. In addition to response trends, cluster calculations also reveal linear additivity in beta(vec) with catenation for all benzoic acid-containing chromophores up to longitudinally aligned trimers. Linear scaling of SHG response with film thickness is observed for benzoic acid-containing chromophores up to 1.0 mu m film thickness.